Overexpression of ameloblastin in secretory ameloblasts results in demarcated, hypomineralized opacities in enamel.

Autor:	Chun YP; Department of Periodontics, School of Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.; Department of Cell Systems and Anatomy, School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.; Department of Molecular Medicine, School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States., Tan C; Department of Periodontics, School of Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States., Villanueva O; Department of Periodontics, School of Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States., Colley ME; Department of Chemistry, University of Texas San Antonio, San Antonio, TX, United States.; Department of Biochemistry, Vanderbilt University, Nashville, TN, United States.; Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN, United States., Quintanilla TJ; Department of Periodontics, School of Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States., Basiouny MS; Department of Periodontics, School of Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States., Hartel CA; Department of Periodontics, School of Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States., Critchfield CS; Department of Periodontics, School of Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States., Bach SBH; Department of Chemistry, University of Texas San Antonio, San Antonio, TX, United States., Fajardo RJ; Department of Clinical and Applied Science Education, School of Osteopathic Medicine, University of the Incarnate Word, San Antonio, TX, United States., Pham CD; Department of Periodontics, School of Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.; Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in physiology [Front Physiol] 2024 Jan 11; Vol. 14, pp. 1233391. Date of Electronic Publication: 2024 Jan 11 (Print Publication: 2023).
DOI:	10.3389/fphys.2023.1233391
Abstrakt:	Introduction: Developmental defects of the enamel manifest before tooth eruption and include amelogenesis imperfecta, a rare disease of underlying gene mutations, and molar-incisor hypomineralization (MIH), a prevalent disease in children originating from environmental and epigenetic factors. MIH enamel presents as the abnormal enamel marked by loss of translucency, demarcation between the healthy and affected enamel, and reduced mineral content. The pathophysiology of opaque, demarcated enamel lesions is not understood; however, the retention of enamel proteins in the matrix has been suggested. Ameloblastin (Ambn) is an enamel protein of the secreted calcium-binding phosphoproteins (SCPPs) critical for enamel formation. When the Ambn gene is mutated or deleted, teeth are affected by hypoplastic amelogenesis imperfecta. Methods: In this study, enamel formation in mice was analyzed when transgenic Ambn was overexpressed from the amelogenin promoter encoding full-length Ambn. Ambn was under- and overexpressed at six increasing concentrations in separate mouse lines. Results: Mice overexpressing Ambn displayed opaque enamel at low concentrations and demarcated lesions at high concentrations. The severity of enamel lesions increased starting from the inner enamel close to the dentino-enamel junction (DEJ) to span the entire width of the enamel layer in demarcated areas. Associated with the opaque enamel were 17-kDa Ambn cleavage products, a prolonged secretory stage, and a thin basement membrane in the maturation stage. Ambn accumulations found in the innermost enamel close to the DEJ and the mineralization front correlated with reduced mineral content. Demarcated enamel lesions were associated with Ambn species of 17 kDa and higher, prolonged secretory and transition stages, a thin basement membrane, and shortened maturation stages. Hypomineralized opacities were delineated against the surrounding mineralized enamel and adjacent to ameloblasts detached from the enamel surface. Inefficient Ambn cleavage, loss of contact between ameloblasts, and the altered basement membrane curtailed the endocytic activity; thus, enamel proteins remained unresorbed in the matrix. Ameloblasts have the ability to distinguish between Ambn concentration and Ambn cleavage products through finely tuned feedback mechanisms. The under- or overexpression of Ambn in murine secretory ameloblasts results in either hypoplastic amelogenesis imperfecta or hypomineralization with opaque or sharply demarcated boundaries of lesions, similar to MIH. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Chun, Tan, Villanueva, Colley, Quintanilla, Basiouny, Hartel, Critchfield, Bach, Fajardo and Pham.)
Databáze:	MEDLINE
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